Promote Motor Function Recovery Research Articles

Chitosan-Modified Hydrogel Microsphere Encapsulating Zinc-Doped Bioactive Glasses for Spinal Cord Injury Repair by Suppressing Inflammation and Promoting Angiogenesis.

Spinal cord injury (SCI) is a common nerve injury caused by external force, resulting in sensory and motor impairments. Previous studies demonstrated that inhibiting the neuroinflammation promoted SCI repair. However, these approaches are low efficient, and lack targeting specificity, and even require repeated and high doses of systemic administration. To address such issues, in the present study, chitosan-modified hydrogel microspheres encapsulating with zinc-doped bioactive glasses (CS-MG@Zn/BGs) is constructed for targeted repair of SCI. In vitro, the CS-MG@Zn/BGs effectively inhibited the acute inflammatory response initiated by microglia and promoted angiogenic activities. In vivo, CS-MG@Zn/BGs targeted the injured site, and attenuated neuroinflammation by inhibiting microglia infiltration and modulating microglia polarization toward M2 type. Furthermore, it facilitated vascular reconstruction, neuronal differentiation, axonal regeneration and remyelination at the injured site, and thereby promoted motor function recovery of SCI mice. The in vitro and in vivo results implied that CS-MG@Zn/BGs may be a promising alternative for the rehabilitation of SCI.

HUCMSC-derived exosomes mitigate blood-spinal cord barrier disruption by activating AMPK/mTOR-mediated autophagic flux after acute spinal cord injury

After spinal cord injury (SCI), the integrity of the blood-spinal cord barrier (BSCB) can be disrupted, leading to the secondary injuries such as inflammatory cell infiltration, neuronal death, and spinal cord hematoma. It is important to maintain the integrity of the BSCB to help restore function following SCI. While some studies have demonstrated the therapeutic effects of exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-exos), their role in preserving BSCB integrity remains unclear. In our study, we demonstrated the protective effects of hUCMSC-exos on the BSCB and its mechanism. The results of this study indicate that hUCMSC-exos promote motor function recovery, preserve spinal cord structure, and reduce neuronal loss by inhibiting BSCB leakage following SCI. Experimental investigations conducted in vivo and in vitro have demonstrated that hUCMSC-exos can mitigate the loss of adherens junctions (AJs) and tight junctions (TJs) and stimulate autophagy in spinal cord endothelial cells. The protective effects were also found to be significantly reversed following the inhibition of autophagy using 3-MA. In conclusion, our study demonstrates that hUCMSC-exos protect the integrity of BSCB by promoting the repair of spinal endothelial cells through activation of autophagy, thereby exerting a protective role in SCI.

Dual-tDCS Ameliorates Cerebral Injury and Promotes Motor Function Recovery via cGAS-STING Signaling Pathway in a Rat Model of Ischemic Stroke.

Ischemic stroke is one of the leading causes of death and disability. Dual transcranial direct current stimulation (dual-tDCS) is a promising intervention to treat ischemic stroke, but its efficacy and underlying mechanism remain to be verified. Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has recently emerged as a key mediator in cerebral injury. However, little is known about the effect of cGAS-STING on neuronal damage in ischemic stroke, and it remains to be studied whether the cGAS-STING pathway is involved in tDCS intervention for ischemic stroke. Therefore, we aimed to investigate whether dual-tDCS can alleviate ischemic brain injury in a rat model of ischemic stroke and if so, whether via cGAS-STING pathway. Middle cerebral artery occlusion (MCAO) was employed to induce a rat model of ischemic stroke. Male SD rats weighing 250-280g were randomly assigned to the Sham, MCAO, Dual-tDCS, Dual-tDCS + RU.521, and Dual-tDCS + 2'3'-cGAMP groups, with 10 rats in each group completing the experiment. Behavioral, morphological, MRI, and molecular biological methods were performed. We found that the cGAS-STING pathway was activated and expressed in neurons after MCAO. Dual-tDCS improved motor function and infarct volume, inhibited neuronal apoptosis, promoted the expression of neurotrophins (BDNF and NGF), CD31, and VEGF, and suppressed inflammation reaction after MCAO via the cGAS-STING pathway. Taken together, dual-tDCS may improve MCAO-induced brain injury and promote the recovery of motor function, resulting from the inhibition of neuronal apoptosis and inflammation reaction, as well as promotion of the expression of nerve plasticity- and angiogenesis-related proteins, via cGAS-STING pathway.

Falcarindiol improves functional recovery and alleviates neuroinflammation after spinal cord injury by inhibiting STAT/MAPK signaling pathways

Spinal cord injury (SCI) is a devastating trauma in the central nervous system (CNS), leading to motor and sensory impairment. Neuroinflammation is one of the critical contributors to the progression of secondary injury. Falcarindiol has been reported to efficaciously mitigate lipopolysaccharide (LPS)-mediated inflammation in RAW 264.7 cells. The role of falcarindiol in SCI recovery remains unclear. In this present study, traumatic SCI mice models and LPS-stimulated murine microglia cell line (BV2 cells) were performed to explore the pharmacological effects and the underlying mechanisms of falcarindiol in improving SCI repair with detection of motor function recovery, morphological changes, numbers of survival neurons and protein expression levels of inflammation or apoptosis-related proteins. Our study found that falcarindiol intervention could promote motor function recovery and reduce spinal cord tissue damage in mice following SCI. Mechanistically, falcarindiol intervention suppressed apoptosis-driven neuronal cell death and mitigated inflammatory reactions following SCI. Additionally, falcarindiol inhibited the activation of signal transducer and activator of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways in vivo and in vitro. This suppression of STAT and MAPK activation by falcarindiol was reversed by STAT3 agonist Colivelin TFA and MAPK agonist C16-PAF in BV2 cells, respectively. Moreover, the study further demonstrated that the anti-inflammation role of falcarindiol was obstructed by Colivelin TFA but not by C16-PAF in LPS-stimulated BV2 cells, suggesting that falcarindiol may efficaciously ameliorate neuroinflammation through inhibiting the activation of STAT signaling pathway following SCI. Collectively, our study indicates that falcarindiol may be a novel drug candidate for the treatment and management of SCI.

Deferoxamine alleviates ferroptosis in seawater immersion combined with traumatic brain injury

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, with its severity potentially exacerbated by seawater immersion. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has been implicated in TBI pathogenesis. However, the specific occurrence and underlying mechanisms of ferroptosis in the context of TBI compounded by seawater immersion remain unclear. Subsequently, we investigated the effects of seawater immersion on ferroptosis after the application of deferoxamine (DFO), an iron chelator and ferroptosis inhibitor, to explore its potential therapeutic value. We conducted RNA sequencing, protein expression analysis, oxidative stress assessment, histopathological examination, and behavioral testing to comprehensively evaluate the impact of DFO on ferroptosis and neurological outcomes. Our results demonstrated that seawater immersion significantly exacerbated ferroptosis in TBI. DFO treatment, however, attenuated ferroptosis, alleviated oxidative stress, reduced brain tissue damage, improved neuronal survival, and promoted motor function recovery. Despite these benefits, DFO exhibited limited effects on anxiety, novel object recognition, and spatial learning and memory. These findings suggest that ferroptosis represents a novel pathological mechanism in TBI under seawater immersion, and that DFO is a promising neuroprotective agent capable of modulating ferroptosis and enhancing neurological function. This study offers new insights into the complex injury conditions associated with TBI and seawater immersion, highlighting the potential of targeting ferroptosis for therapeutic intervention.

Berberine attenuates neuronal ferroptosis via the AMPK–NRF2–HO-1-signaling pathway in spinal cord-injured rats

Ferroptosis, characterized by iron-dependent accumulation of lipid peroxides, plays an important role in spinal cord injury (SCI). Berberine (BBR), as a lipid peroxide scavenger, has been widely used in treating other diseases; however, its role in ferroptosis has not been fully elucidated. Therefore, here, to test our hypothesis that BBR can reduce the severity of SCI and promote motor function recovery by inhibiting neuronal ferroptosis, we evaluated the changes in ferroptosis-related indicators after BBR administration by establishing a cellular ferroptosis model and an SCI contusion model. We found that BBR administration significantly reduces lipid peroxidation damage, maintains normal mitochondrial function, reduces excessive accumulation of iron ions, enhances antioxidant capacity, and activates the ferroptosis defense system in vivo and in vitro. Mechanistically, BBR alleviates neuronal ferroptosis by inducing adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and up-regulating nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) protein expression to promote glutathione production. BBR administration also significantly improves motor function recovery in SCI rats. Meanwhile, applying the AMPK inhibitor Compound C blocks the neuroprotective and all other effects of BBR. Collectively, our findings demonstrate that BBR can attenuate neuronal ferroptosis after SCI by activating the AMPK–NRF2–HO-1 pathway.

ARL11 knockdown alleviates spinal cord injury by inhibiting neuroinflammation and M1 activation of microglia in mice

Spinal cord injury (SCI) is a severe central nervous system injury and microglia are major participants in neuroinflammation after injury. ADP-ribosylation factor-like GTPase 11 (ARL11) is a GTP-binding protein. Whether ARL11 is involved in the SCI progression is unknown. In the impactor-induced moderate SCI mouse model, ARL11 protein and mRNA expression were significantly increased in the injury site. LPS (100 ng/mL) and IFN-γ (20 ng/mL) were incubated with BV2 cells (immortalized mouse microglial cell line) to drive them into an M1-like phenotype. ARL11 up-regulation was also observed in activated microglia in SCI mice and LPS and IFN-γ treated BV2 cells. Basso Mouse Scale scores and inclined plate test revealed that ARL11 deletion promoted motor function recovery in SCI mice. Pathological examination showed ARL11 knockdown reduced spinal cord tissue damage, increased neuron numbers, and inhibited neuronal apoptosis in SCI mice. ARL11 knockdown notably inhibited IL-1β and IL-6 production in vivo and in vitro. Furthermore, ARL11 deletion significantly inhibited iNOS protein and mRNA expression in vivo and in vitro, and COX-2 expression in vivo. Mechanism studies revealed that ARL11 silencing decreased phosphorylated ERK1/2 protein expression. Additionally, ELF1 knockdown significantly inhibited ARL11 protein and mRNA expression in vitro. ELF1 acted as a transcription activator in regulating ARL11 expression by binding to the promoter. In conclusion, ARL11 knockdown protects neurons by inhibiting M1 microglia-induced neuroinflammation, thereby promoting motor functional recovery in SCI mice. This may occur in part under the regulation of ELF1. Our study provides a new molecular target for SCI treatment.

High-frequency magnetic paired associated stimulation promotes motor function recovery in ischemic stroke patients: a study protocol for single-center, sham stimulation randomized controlled trials (H2MPAS)

BackgroundNumerous studies have validated the clinical effectiveness of electromagnetic pairing-associated stimulation. Building upon this foundation, we have developed a novel approach involving high-frequency magnetic paired-associated stimulation, aiming to enhance clinical applicability and potentially improve efficacy. However, the clinical effectiveness of this approach remains unclear. Our objective is to demonstrate the therapeutic efficacy of this novel approach by employing high-frequency pairing to intervene in patients experiencing motor dysfunction following a stroke.MethodsThis is a single-center, single-blind, sham stimulation controlled clinical trial involving patients with upper limb motor dysfunction post-stroke. The intervention utilizes paired magnetic stimulation, combining peripheral and central magnetic stimulation, in patients with Brunnstrom stage III–V stroke lasting from 3 months to 1 year. Evaluation of patients’ upper limb motor function occurred before the intervention and after 3 weeks of intervention. Follow-up visits will be conducted after 5 weeks and 3 months of intervention. The primary outcome measure is the Action Research Arm Test, with secondary measures including the Fugl-Meyer Assessment-upper, Modified Barthel Index, modified Tardieu scale, functional near-infrared spectroscopy, and neuroelectrophysiology.DiscussionThe high-frequency magnetic paired associative stimulation used in this study combined high-frequency magnetic stimulation with paired stimulation, potentially facilitating both cortical excitation through high-frequency stimulation and specific circuit enhancement through paired stimulation. As dual-coil magnetic stimulation equipment becomes increasingly popular, magnetic-magnetic paired associated stimulation may offer patients improved clinical outcomes at reduced costs.Trial registrationChinese Clinical Trial Registry,ChiCTR2400083363. Registered on 23 April 2024.

The therapeutic potential of fibroblast growth factors in spinal cord injury: Roles and applications for neuroprotection

Spinal cord injury (SCI) is a severe and debilitating condition that often leads to significant and permanent neurological deficits, affecting motor, sensory, and autonomic functions. The high prevalence of SCI and the lack of effective treatments make it a critical area of medical research. Recent studies have shown promising prospects for fibroblast growth factors (FGF) in the treatment of SCI. FGF, particularly FGF-1 and FGF-2, are known to promote cell growth, differentiation, and survival, and have been demonstrated to enhance axonal regeneration and functional recovery in SCI models. This review highlights the roles of various FGF in neuroprotection, axonal regeneration, and remyelination. It also discusses the potential therapeutic applications of FGF in SCI treatment, emphasizing their ability to reduce neuroinflammation, oxidative stress, and promote motor function recovery. The comprehensive overview of existing research underscores the importance of FGF in SCI repair and suggests further exploration into their therapeutic potential.

Screening strategy identified idebenone loaded ROS-responsive nano-polyphenolic vesicle for spinal cord injury therapy

Spinal cord injury (SCI) is a severe central nerve diseases which lacks effective of treatment. Oxidative stress is a major pathological factor for SCI. It may induce mitochondrial damage, which further lead to ferroptosis and apoptosis in neural cells during SCI. Thus, targeting oxidative stress may be the key strategy for SCI treatment. In this study, we carried out screening experiment in the natural product library against oxidative stress in neural cells. It was identified that idebenone (IDE) may potently suppress oxidative stress induced cell death in neural cells. Furthermore, we successfully developed a multifunctional nanovesicles, which we named IDE@PPNs, by encapsulating IDE within proanthocyanidin polyphenol nanovesicles (PPNs). IDE@PPNs exhibited lysosomal escape capability and mitochondrial ROS responsiveness; meanwhile, they may suppress ferroptosis and apoptosis in neural cells. In vivo study demonstrated that IDE@PPNs may promote motor function recovery in rats and suppress ferroptosis and apoptosis in neurons. It may also show high biocompatibility in in vivo study. In summary, we fabricated a novel natural product loaded ROS responsive nanovesicles, IDE@PPNs may have the great potential for SCI therapy.

Inhibition of UHRF1 Improves Motor Function in Mice with Spinal Cord Injury

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.Graphical Downregulation of UHRF1 promotes the recovery of motor function in mice with spinal cord injury. By analyzing the RNA sequencing results of mice with spinal cord injury for 3 days and selecting UHRF1 for experimental validation, the study found that inhibiting UHRF1 can promote motor function recovery.

MSC-derived exosomes deliver ZBTB4 to mediate transcriptional repression of ITIH3 in astrocytes in spinal cord injury

BackgroundBMSC-secreted exosomes (BMSC-Exos) have shown potential for promoting behavioral recovery following spinal cord injury (SCI). However, its role in blocking astrocyte activation remains unclear. Thus, this study aimed to determine whether BMSC-Exos impair the function of astrocytes following SCI in mice and to seek the mechanism. MethodsBMSC-Exos were collected by ultracentrifugation and identified. The SCI mice were developed by laminectomy combined with spinal cord shock, followed by BMSC-Exos or nerve growth factor (positive control) treatment. HE staining, Nissl staining, and TUNEL were conducted to analyze the pathological structural damage and neuronal damage in the mouse spinal cord. Bioinformatics was used to screen altered molecules under the BMSC-Exos treatment. Effects of BMSC-Exos and changes in ZBTB4 and ITIH3 expression on neuronal damage induced by activated astrocytes in the co-culture system were analyzed by CCK-8 and flow cytometry. ResultsNerve growth factor and BMSC-Exos promoted motor function recovery, alleviated nerve injury, and reduced apoptosis in mice with SCI. ZBTB4 was enriched in BMSC-Exos and lowly expressed in SCI. Downregulation of ZBTB4 diminished the therapeutic effects of BMSC-Exos against SCI. ITIH3 was a downstream target of ZBTB4. Neurotoxic activation of astrocytes induced neuronal injury, which was alleviated by BMSC-Exos. However, ZBTB4 knockdown overturned the effects of BMSC-Exos in vitro and combined ITIH3 knockdown alleviated the accentuating effects of ZBTB4 knockdown on neuronal injury. ConclusionBMSC-Exos protected against astrocyte-induced neuronal injury by delivering ZBTB4 to repress ITIH3, ultimately improving motor function in mice with SCI.

Decellularized extracellular matrix enriched with GDNF enhances neurogenesis and remyelination for improved motor recovery after spinal cord injury

Motor functional improvement represents a paramount treatment objective in the post-spinal cord injury (SCI) recovery process. However, neuronal cell death and axonal degeneration following SCI disrupt neural signaling, impeding the motor functional recovery. In this study, we developed a multifunctional decellularized spinal cord-derived extracellular matrix (dSECM), crosslinked with glial cell-derived neurotrophic factor (GDNF), to promote differentiation of stem cells into neural-like cells and facilitate axonogenesis and remyelination. After decellularization, the immunogenic cellular components were effectively removed in dSECM, while the crucial protein components were retained which supports stem cells proliferation and differentiation. Furthermore, sustained release of GDNF from the dSECM facilitated axonogenesis and remyelination by activating the PI3K/Akt and MEK/Erk pathways. Our findings demonstrate that the dSECM-GDNF platform promotes neurogenesis, axonogenesis, and remyelination to enhance neural signaling, thereby yielding promising therapeutic effects for motor functional improvement after SCI. Statement of significanceThe dSECM promotes the proliferation and differentiation of MSCs or NSCs by retaining proteins associated with positive regulation of neurogenesis and neuronal differentiation, while eliminating proteins related to negative regulation of neurogenesis.After crosslinking, GDNF can be gradually released from the platform, thereby promoting neural differentiation, axonogenesis, and remyelination to enhance neural signaling through activation of the PI3K/Akt and MEK/Erk pathways.In vivo experiments demonstrated that dSECM-GDNF/MSC@GelMA hydrogel exhibited the ability to facilitate neuronal regeneration at 4 weeks post-surgery, while promoting axonogenesis and remyelination at 8 weeks post-surgery, ultimately leading to enhanced motor functional recovery.This study elucidates the ability of neural regeneration strategy to promote motor functional recovery and provides a promising approach for designing multifunctional tissue for SCI treatment.

FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival.

JOURNAL/nrgr/04.03/01300535-202507000-00031/figure1/v/2024-09-09T124005Z/r/image-tiff FK506 (Tacrolimus) is a systemic immunosuppressant approved by the U.S. Food and Drug Administration. FK506 has been shown to promote peripheral nerve regeneration, however, its precise mechanism of action and its pathways remain unclear. In this study, we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve, increased the numbers of motor and sensory neurons, reduced inflammatory responses, markedly improved the conduction function of the injured nerve, and promoted motor function recovery. These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

Inhibition of aquaporin-4 and its subcellular localization attenuates below-level central neuropathic pain by regulating astrocyte activation in a rat spinal cord injury model

The mechanisms of central neuropathic pain (CNP) caused by spinal cord injury have not been sufficiently studied. We have found that the upregulation of astrocytic aquaporin-4 (AQP4) aggravated peripheral neuropathic pain after spinal nerve ligation in rats. Using a T13 spinal cord hemisection model, we showed that spinal AQP4 was markedly upregulated after SCI and mainly expressed in astrocytes in the spinal dorsal horn (SDH). Inhibition of AQP4 with TGN020 suppressed astrocyte activation, attenuated the development and maintenance of below-level CNP and promoted motor function recovery in vivo. In primary astrocyte cultures, TGN020 also changed cell morphology, diminished cell proliferation and suppressed astrocyte activation. Moreover, T13 spinal cord hemisection induced cell-surface abundance of the AQP4 channel and perivascular localization in the SDH. Targeted inhibition of AQP4 subcellular localization with trifluoperazine effectively diminished astrocyte activation in vitro and further ablated astrocyte activation, attenuated the development and maintenance of below-level CNP, and accelerated functional recovery in vivo. Together, these results provide mechanistic insights into the roles of AQP4 in the development and maintenance of below-level CNP. Intervening with AQP4, including targeting AQP4 subcellular localization, might emerge as a promising agent to prevent chronic CNP after SCI.

The identification of new roles for nicotinamide mononucleotide after spinal cord injury in mice: an RNA-seq and global gene expression study.

Nicotinamide mononucleotide (NMN), an important transforming precursor of nicotinamide adenine dinucleotide (NAD+). Numerous studies have confirmed the neuroprotective effects of NMN in nervous system diseases. However, its role in spinal cord injury (SCI) and the molecular mechanisms involved have yet to be fully elucidated. We established a moderate-to-severe model of SCI by contusion (70 kdyn) using a spinal cord impactor. The drug was administered immediately after surgery, and mice were intraperitoneally injected with either NMN (500 mg NMN/kg body weight per day) or an equivalent volume of saline for seven days. The central area of the spinal cord was harvested seven days after injury for the systematic analysis of global gene expression by RNA Sequencing (RNA-seq) and finally validated using qRT-PCR. NMN supplementation restored NAD+ levels after SCI, promoted motor function recovery, and alleviated pain. This could potentially be associated with alterations in NAD+ dependent enzyme levels. RNA sequencing (RNA-seq) revealed that NMN can inhibit inflammation and potentially regulate signaling pathways, including interleukin-17 (IL-17), tumor necrosis factor (TNF), toll-like receptor, nod-like receptor, and chemokine signaling pathways. In addition, the construction of a protein-protein interaction (PPI) network and the screening of core genes showed that interleukin 1β (IL-1β), interferon regulatory factor 7 (IRF 7), C-X-C motif chemokine ligand 10 (Cxcl10), and other inflammationrelated factors, changed significantly after NMN treatment. qRT-PCR confirmed the inhibitory effect of NMN on inflammatory factors (IL-1β, TNF-α, IL-17A, IRF7) and chemokines (chemokine ligand 3, Cxcl10) in mice following SCI. The reduction of NAD+ levels after SCI can be compensated by NMN supplementation, which can significantly restore motor function and relieve pain in a mouse model. RNA-seq and qRT-PCR systematically revealed that NMN affected inflammation-related signaling pathways, including the IL-17, TNF, Toll-like receptor, NOD-like receptor and chemokine signaling pathways, by down-regulating the expression of inflammatory factors and chemokines.

Pericyte-derived exosomal miR-210 improves mitochondrial function and inhibits lipid peroxidation in vascular endothelial cells after traumatic spinal cord injury by activating JAK1/STAT3 signaling pathway

BackgroundSpinal cord injury (SCI) remains a significant health concern, with limited available treatment options. This condition poses significant medical, economic, and social challenges. SCI is typically categorized into primary and secondary injuries. Inflammation, oxidative stress, scar formation, and the immune microenvironment impede axon regeneration and subsequent functional restoration. Numerous studies have shown that the destruction of the blood–brain barrier (BBB) and microvessels is a crucial factor in severe secondary injury. Additionally, reactive oxygen species (ROS)-induced lipid peroxidation significantly contributes to endothelial cell death. Pericytes are essential constituents of the BBB that share the basement membrane with endothelial cells and astrocytes. They play a significant role in the establishment and maintenance of BBB.ResultsImmunofluorescence staining at different time points revealed a consistent correlation between pericyte coverage and angiogenesis, suggesting that pericytes promote vascular repair via paracrine signaling. Pericytes undergo alterations in cellular morphology and the transcriptome when exposed to hypoxic conditions, potentially promoting angiogenesis. We simulated an early ischemia-hypoxic environment following SCI using glucose and oxygen deprivation and BBB models. Co-culturing pericytes with endothelial cells improved barrier function compared to the control group. However, this enhancement was reduced by the exosome inhibitor, GW4869. In vivo injection of exosomes improved BBB integrity and promoted motor function recovery in mice following SCI. Subsequently, we found that pericyte-derived exosomes exhibited significant miR-210-5p expression based on sequencing analysis. Therefore, we performed a series of gain- and loss-of-function experiments in vitro.ConclusionOur findings suggest that miR-210-5p regulates endothelial barrier function by inhibiting JAK1/STAT3 signaling. This process is achieved by regulating lipid peroxidation levels and improving mitochondrial function, suggesting a potential mechanism for restoration of the blood-spinal cord barrier (BSCB) after SCI.

Self-Supervised EEG Representation Learning with Contrastive Predictive Coding for Post-Stroke Patients.

Stroke patients are prone to fatigue during the EEG acquisition procedure, and experiments have high requirements on cognition and physical limitations of subjects. Therefore, how to learn effective feature representation is very important. Deep learning networks have been widely used in motor imagery (MI) based brain-computer interface (BCI). This paper proposes a contrast predictive coding (CPC) framework based on the modified s-transform (MST) to generate MST-CPC feature representations. MST is used to acquire the temporal-frequency feature to improve the decoding performance for MI task recognition. EEG2Image is used to convert multi-channel one-dimensional EEG into two-dimensional EEG topography. High-level feature representations are generated by CPC which consists of an encoder and autoregressive model. Finally, the effectiveness of generated features is verified by the k-means clustering algorithm. It can be found that our model generates features with high efficiency and a good clustering effect. After classification performance evaluation, the average classification accuracy of MI tasks is 89% based on 40 subjects. The proposed method can obtain effective feature representations and improve the performance of MI-BCI systems. By comparing several self-supervised methods on the public dataset, it can be concluded that the MST-CPC model has the highest average accuracy. This is a breakthrough in the combination of self-supervised learning and image processing of EEG signals. It is helpful to provide effective rehabilitation training for stroke patients to promote motor function recovery.

High rapamycin-loaded hollow mesoporous Prussian blue nanozyme targets lesion area of spinal cord injury to recover locomotor function

Scavenging free radicals and reducing inflammatory reaction to relieve the secondary damage are important issues in the spinal cord injury (SCI) therapeutic strategy. Nanozymes attract more attention in the drug development of SCI due to the high stability, long-lasting catalytic capacity, and multienzyme-like properties. Herein, we constructed a Rapamycin (Rapa)-loaded and hollow mesoporous Prussian blue (HMPB)-based nanozyme (RHPAzyme) to realize the combined antioxidation and anti-inflammation combination therapy of SCI. Furthermore, activated cell penetrating peptide (ACPP) is modified onto nanozyme to endow the effectively ability of lesion area-targeting. This RHPAzyme exhibits ROS scavenging capacity with the transformation of Fe2+/Fe3+ valance and cyanide group of HMPB to achieve multienzyme-like activity. As expected, RHPAzyme scavenges the ROS overproduction and reduces inflammation in oxygen-glucose deprivation (OGD)-induced damage via inhibiting MAPK/AKT signaling pathway. Furtherly, RHPAzyme exhibits the combined antioxidant and anti-inflammatory activity in vivo, which can effectively alleviate neuronal damage and promote motor function recovery in SCI mice. Overall, this study demonstrates the RHPAzyme induces an effective treatment of SCI by inhibiting oxygen-mediated cell apoptosis and suppressing inflammation-induced injury, thus reduces the nervous impairment and promotes motor function recovery.

Glycine and N-Acetylcysteine (GlyNAC) Combined with Body Weight Support Treadmill Training Improved Spinal Cord and Skeletal Muscle Structure and Function in Rats with Spinal Cord Injury.

Skeletal muscle atrophy is a frequent complication after spinal cord injury (SCI) and can influence the recovery of motor function and metabolism in affected patients. Delaying skeletal muscle atrophy can promote functional recovery in SCI rats. In the present study, we investigated whether a combination of body weight support treadmill training (BWSTT) and glycine and N-acetylcysteine (GlyNAC) could exert neuroprotective effects, promote motor function recovery, and delay skeletal muscle atrophy in rats with SCI, and we assessed the therapeutic effects of the double intervention from both a structural and functional viewpoint. We found that, after SCI, rats given GlyNAC alone showed an improvement in Basso-Beattie-Bresnahan (BBB) scores, gait symmetry, and results in the open field test, indicative of improved motor function, while GlyNAC combined with BWSTT was more effective than either treatment alone at ameliorating voluntary motor function in injured rats. Meanwhile, the results of the skeletal muscle myofiber cross-sectional area (CSA), hindlimb grip strength, and acetylcholinesterase (AChE) immunostaining analysis demonstrated that GlyNAC improved the structure and function of the skeletal muscle in rats with SCI and delayed the atrophication of skeletal muscle.